Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature

Purpose of review.
Glioblastoma is the commonest primary brain cancer in adults whose outcomes are amongst the worst of any cancer. The current treatment pathway comprises surgery and postoperative chemoradiotherapy whereby unresectable diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis. Intratumoural heterogeneity combined with increased hypoxia in the postoperative tumour microenvironment potentially decreases the efficacy of adjuvant interventions and fails to prevent early postoperative regrowth, called rapid early progression (REP). In this review we discuss the clinical implication and the biological and clinical foundations of post-surgery REP. Subsequently, clinical interventions potentially targeting this phenomenon are reviewed systematically.

Recent findings.
Early interventions include early systemic chemotherapy, neoadjuvant immunotherapy, local therapies delivered during surgery (including Gliadel wafers, nanoparticles and stem cell therapy) and several radiotherapy techniques. We critically appraise these different strategies in terms of their efficacy, toxicity, challenges and potential to prolong survival. Finally, we discuss potential interventional leads moving forward to improve the outcome of patients with glioblastoma.

Summary.
There is biological rationale to suggest that early interventions could benefit the outcome of glioblastoma patients and they should be investigated in future trials.

Keywords
Glioblastoma; radiotherapy; intraoperative radiotherapy; radiation; brachytherapy; neoadjuvant, neurosurgery; pre-operative; progression; stem cells; Gliadel; immunotherapy; radiosurgery